2-Fluoro-4,6-dichlorobenzoic acid

124-38-9

904285-09-2

General procedure for the synthesis of 2,4-dichloro-6-fluorobenzoic acid from carbon dioxide: Part A. Synthesis of 2,4-dichloro-6-fluorobenzoic acid: To anhydrous THF (100 mL), a hexane solution of 2.5 M n-butyllithium (8.72 mL, 21.8 mmol) was slowly added at -78 °C and under nitrogen protection, followed by a THF solution of 1.0 M potassium tert-butoxide (21.81 mL, 21.8 mmol). After the reaction mixture was stirred at -78 °C for 30 min, 3,5-dichlorofluorobenzene (3.0 g, 18.2 mmol) was added dropwise over a period of 10 min and stirring was continued at -78 °C for 40 min. Subsequently, carbon dioxide gas was passed into the reaction mixture for 10 minutes. After the reaction mixture was slowly warmed to room temperature, it was diluted with ether (100 mL) and extracted with 1.0 M aqueous sodium hydroxide solution (2 x 50 mL). The combined sodium hydroxide extracts were washed with ether (100 mL), acidified to pH 3 with concentrated aqueous hydrochloric acid, and extracted with ethyl acetate (2 × 50 mL). The combined ethyl acetate layers were dried over anhydrous sodium sulfate and concentrated. The crude product was purified by ISCO fast chromatography (silica gel column, eluent 100:0 to 0:100 hexane-ethyl acetate gradient) to afford the title compound 2,4-dichloro-6-fluorobenzoic acid as a brown solid (1.34 g, 35% yield).